This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Injury is a well established risk factor in the pathogenesis of osteoarthritis (OA). Several large longitudinal population studies support this observation based upon patient history and retrospective data collection instruments. However, efforts to identify patients at risk of progression have been limited. We posit that patients with acute knee injuries and resultant inflammation are at risk for early wear and damage to articular cartilage due to loss of lubricating ability. These patients present to emergency departments and manifest an acute traumatic synovitis (TS) secondary to acute structural defects such as acute anterior cruciate ligament (ACL) injuries following trauma. These patients are young and feature, 1) collagen type II fragment release consistent with early cartilage destruction, 2) digestion of lubricin (PRG4) and lack lubricating ability, and 3) do not have any history of degenerative joint disease. We argue that inflammation results in the destruction of lubricin, accompanied by the fibrillation of cartilage and chronic symptoms which underpin the population based observation of early OA attributable to joint injury. Interventions intended to address some of the earliest causative factors of OA could be emergency department (ED) or primary care based. There may also be a critical time window immediately after a joint injury when limiting the extent of this process could be a primary therapeutic endpoint. The aims are the following: Aim 1: To Investigate the Early Effects of an ACL Injury on Lubricating Mechanisms Mediated by Lubricin in a Mammalian Joint. Hypothesis: An ACL injury induced in rat knee joints results in changes to lubricin metabolism leading to an elevation of the coefficient of friction ([unreadable]) of the joint. This results in permanent damage to articulating surfaces or failure of the joint to return to a low [unreadable] of 0.001. Aim 2: Blocking the Effects of TNF-[unreadable] Through the Administration of a TNF-[unreadable] Inhibitor Partially Restores the Lubricating Ability of Diarthrodial Joints Following ACL Injury. Hypothesis: TNF-[unreadable] play a significant role in mediating changes in lubricin metabolism following ACL injury. Blocking the effects of TNF-[unreadable] preserves joint lubrication and limits joint wear. Aim 3: Synovial Fluid Aspirates from Patients with Acute ACL Injuries will be Analyzed for IL-1 and TNF-[unreadable]. Hypothesis: An inverse relationship exists between lubricin concentration and catabolic cytokines in clinical aspirates which can be characterized as a mild inflammatory state.